Owing to the lack of cell walls and/or extra cellular materials the culture of eukaryotic cells, animal cells, mammalian cells, and/or tissue is more difficult and more complex because these cells are far more delicate and fragile than microbial cells. The most commonly used device for these cells is the mechanically agitated bioreactor which employs a low shear agitator or applies sparging of air or oxygen to promote the gas-liquid mixing and to provide sufficient oxygen supply to the cells in the culture medium with minimum shear stress. This type of bioreactor, however, is not easy to scale up because the shear distribution is scale-dependent. Adherent cells are always required to attach to some carrier for growth. T-Flasks and roller bottles are the most commonly used devices for these types of cell cultures, but they are extremely labor intensive and lack control capability, and are therefore not economical for large scale production. The microcarrier bioreactor is another common device for these types of cell cultures which substantially increases surface area for cells to attach. The microcarrier bioreactor however requires constant agitation to suspend the microcarrier particles resulting in exposing the sensitive cells to shear stress and low loading capacity of microcarriers. The shear stress environment under agitation is also not favorable for cell attachment and/or virus infection. It is also difficult to separate the attached cells from the medium for frequent medium replacement, making it difficult to operate and incapable of achieving high cell density and is thus less efficient for production.
All of the packed bed bioreactors available on the market utilize macro-porous fiber as a fixed packed bed and use mechanical agitation or a circulation pump to circulate the media through the bed to replenish the nutrients and oxygen. All fixed bed bioreactors that have the bed submerged in the medium rely solely upon the limited pumping force to achieve limited oxygenation for the embedded cells. As a result, these bioreactors have limitations of scalability. Additionally, these fixed bed bioreactors lack the mobility of the bed, limiting the functionality of cell attachment and detachment, cell distribution along the bed, and virus infection.
Another type of bioreactor which is used for solid state fermentation applications is a horizontally rocked fermenter system. The majority of medium components in this bioreactor are solid which is mixed inside the horizontal vessel using its rocking and tumbling motion of the vessel to perform the aerobic or anaerobic fermentation under humidity control. This bioreactor however cannot be used for cell culture wherein the majority is liquid culture material because its rocking motion can only generate little or no mixing effect on liquid culture material even at high rocking rate for sufficient aeration and oxygenation for cell cultures.
Another horizontally rotated bioreactor uses a horizontally rotated vessel using a coaxial membrane tube as an oxygenator for cell cultures. This bioreactor has been used for a wide range of cell culture applications for research and development use. However, due to the limited membrane area and capability of oxygen transfer, this type of bioreactor can only be limited to small scale applications. It has therefore never been applied in large scale application.